Constitutive expression of the neuron-restrictive silencer factor (NRSF)/REST in differentiating neurons disrupts neuronal gene expression and causesaxon pathfinding errors in vivo

The neuron-restrictive silencer factor (NRSF; also known as REST for repres sor element-1 silencing transcription factor) is a transcriptional represso r of multiple neuronal genes, but little is known about its function in viv o. NRSF is normally down-regulated upon neuronal differentiation. Constitut ive expression of NRSF in the developing spinal cord of chicken embryos cau sed repression of two endogenous target genes, N-tubulin and Ng-CAM, but di d not prevent overt neurogenesis. Nevertheless, commissural neurons that di fferentiated while constitutively expressing NRSF showed a significantly in creased frequency of axon guidance errors. These data suggest that down-reg ulation of NRSF is necessary for the proper development of at least some cl asses of neurons in vivo.